TE1PA as Innovating Chelator for 64Cu Immuno-TEP Imaging: A Comparative in Vivo Study with DOTA/NOTA by Conjugation on 9E7.4 mAb in a Syngeneic Multiple Myeloma Model
العنوان: | TE1PA as Innovating Chelator for 64Cu Immuno-TEP Imaging: A Comparative in Vivo Study with DOTA/NOTA by Conjugation on 9E7.4 mAb in a Syngeneic Multiple Myeloma Model |
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المؤلفون: | Alain Faivre-Chauvet, Raphaël Tripier, Nathalie Le Bris, Thomas Le Bihan, Patricia Le Saëc, Mickaël Bourgeois, Clément Bailly, Catherine Saï-Maurel, Michel Chérel, Anne-Sophie Navarro |
المساهمون: | Nuclear Oncology (CRCINA-ÉQUIPE 13), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Chimie, Electrochimie Moléculaires et Chimie Analytique (CEMCA), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC), Cyclotron ARRONAX [Saint-Herblain], ARRONAX - (GIP) Groupement d'Intérêt Public [Saint-Herblain] (Institut de Recherche Public), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université de Brest (UBO)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Bernardo, Elizabeth |
المصدر: | Bioconjugate Chemistry Bioconjugate Chemistry, American Chemical Society, 2019, ⟨10.1021/acs.bioconjchem.9b00510⟩ Bioconjugate Chemistry, 2019, ⟨10.1021/acs.bioconjchem.9b00510⟩ |
بيانات النشر: | American Chemical Society (ACS), 2019. |
سنة النشر: | 2019 |
مصطلحات موضوعية: | Biodistribution, medicine.drug_class, Biomedical Engineering, Pharmaceutical Science, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bioengineering, 02 engineering and technology, Monoclonal antibody, 01 natural sciences, chemistry.chemical_compound, [SDV.CAN] Life Sciences [q-bio]/Cancer, In vivo, medicine, DOTA, ComputingMilieux_MISCELLANEOUS, Pharmacology, biology, 010405 organic chemistry, Chemistry, Organic Chemistry, 021001 nanoscience & nanotechnology, Ligand (biochemistry), In vitro, 0104 chemical sciences, Cell culture, biology.protein, Cancer research, Antibody, 0210 nano-technology, Biotechnology |
الوصف: | Following the successful synthesis of a C-functionalized version of the TE1PA ligand, a monopicolinate cyclam, we looked to demonstrate its in vivo properties versus DOTA and NOTA, after conjugation on the 9E7.4 rat antibody, an IgG2a against CD138 murine, which has relevant properties for multiple myeloma targeting. For each ligand, different conjugation approaches had been considered to select the most appropriate for the comparative study. The p-SCN-Bn-TE1PA, NHS-DOTA, and p-SCN-Bn-NOTA were finally chosen for conjugation and radiolabeling tests. For in vivo comparison, we used a model of subcutaneous grafted mice with 5T33 tumor cells. In vitro tests and immuno-PET study highlighted 64Cu-9E7.4-p-SCN-Bn-NOTA as the least attractive. Further competitive biodistribution and hepatic metabolic studies at 2, 24, and 48 h post-injection (100 μg radiolabeled with 10 MBq of 64Cu) were then performed with the 64Cu-9E7.4-p-SCN-Bn-TE1PA and 64Cu-9E7.4-NHS-DOTA. Results show a better in vivo resistance of 64Cu-9E7.4-p-SCN-Bn-TE1PA to transchelation compared to 64Cu-9E7.4-NHS-DOTA, especially at later times. This was confirmed with 64Cu-9E7.4-p-SCN-Bn-NOTA at 48 h PI. 64Cu-9E7.4-p-SCN-Bn-TE1PA also demonstrated an excellent hepatic clearance. 64Cu-9E7.4-p-SCN-Bn-TE1PA displayed an overall superiority compared to 64Cu-9E7.4-NHS-DOTA and 64Cu-9E7.4-p-SCN-Bn-NOTA in terms of in vivo stability, reinforcing the usefulness of the p-SCN-Bn-TE1PA ligand for 64Cu immuno-PET imaging. |
وصف الملف: | application/pdf |
تدمد: | 1520-4812 1043-1802 |
DOI: | 10.1021/acs.bioconjchem.9b00510 |
DOI: | 10.1021/acs.bioconjchem.9b00510⟩ |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::452fdfced73895e7f761ab6997f37215 https://doi.org/10.1021/acs.bioconjchem.9b00510 |
Rights: | EMBARGO |
رقم الانضمام: | edsair.doi.dedup.....452fdfced73895e7f761ab6997f37215 |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15204812 10431802 |
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DOI: | 10.1021/acs.bioconjchem.9b00510 |